Pancreatic cancer is a highly lethal disease that is very difficult to diagnose and treat. The effective treatment of pancreatic cancer is critically relying on the diagnosis of the disease at an early stage. Because the current methods for diagnosing very early pancreatic cancer are ineffective, there is an urgent need for new biomarkers. These biomarkers would be particularly useful in patients who are at increased risk of developing pancreatic cancer and who have an abnormal pancreas because of chronic pancreatitis or cystic lesions. Such lesions can be difficult to manage because of the uncertainty regarding neoplastic progression. Pancreatic juice is a proximal body fluid and represents an opportune specimen for identifying biomarkers of pancreatic cancer. Cancer cells are preferentially shed into the ductal lumen, making juice a rich source of cancer associated markers. In the past few years, a large number of pancreatic cancer biomarker candidates have been identified by proteomics and other techniques. Validation of these biomarker candidates is an important step to close the gap between bench research and clinical application, and has been the major bottleneck for biomarker development for pancreatic cancer diagnosis. In the proposed study, we plan to characterize a selected group of pancreatic cancer biomarker candidates for their performance in pancreatic juice for pancreatic cancer detection. Our patient cohort will include those with cancer and the early stages of pre-cancer versus diseased controls with cystic lesions and pancreatitis. A complementary approach of biomarker development will combine state-of-the-art immunoassays and targeted proteomic assays. These assays will be applied to evaluate the protein candidates in clinical pancreatic juice specimens. Biomarkers developed from this study could be used to aide in assessment of high-risk patients undergoing endoscopic procedures. It is also possible that these biomarkers could be further developed into blood based test for early detection of pancreatic cancer.